Specific TaqMan allelic discrimination assay for rs1477196 and rs9939609 single nucleotide polymorphisms of FTO gene demonstrated that there is no association between these SNPs and risk of breast cancer in Iranian women

Authors

1 Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, and Medical Genetics Center of Genome, Shariati St., Isfahan, Iran

2 Department of Clinical Oncology, Medical School, Isfahan University of Medical Sciences, Isfahan, and Medical Genetics Center of Genome, Shariati St., Isfahan, Iran

3 Department of Medical Genetics, Medical School, Isfahan University of Medical Sciences, Isfahan, and Medical Genetics Center of Genome, Shariati St., Isfahan, Iran

Abstract

Background: Breast cancer (BC), is the most common cancer in women, that is the major cause of cancer-related morbidity and mortality in women. Obesity is considered as a major risk factor for BC that increases both the rate and intensity of the disease. Polymorphisms in FTO gene, a known obesity related gene, is shown to be associated with obesity-related traits as well. The aim of this study was to evaluate the association between previously reported single nucleotide polymorphisms (SNPs) of intron 1of FTO gene, rs1477196 and rs9939609 and risk of BC in a subset of Iranian BC patients.
Materials and Methods: We genotyped 99 cases and 100 controls for the two SNPs of rs9939609 and rs1477196 by TaqMan allelic discrimination assay. For each sample in an allelic discrimination assay, a unique pair of fluorescent dye probe is used. One fluorescent dye probe has a perfect match with the wild type allele and the other fluorescent dye probe is perfectly matched to the mutated allele.
Results: Our research has shown that the observed differences between case and control groups in the studied SNPs of FTO gene are not statistically significant (P > 0.05).
Conclusions: Our findings suggest that there is no association between rs9939609 and rs1477196 polymorphisms in FTO gene and increase in risk of BC in the studied Iranian population. These results were inconsistent with that of previously reported case-control studies with BC that means presence of these polymorphisms depends on ethnic group.

Keywords

1.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012;62:10-29.  Back to cited text no. 1
    
2.
Hajian-Tilaki KO, Gholizadehpasha AR, Bozorgzadeh S, Hajian-Tilaki E. Body mass index and waist circumference are predictor biomarkers of breast cancer risk in Iranian women. Med Oncol 2011;28:1296-301.  Back to cited text no. 2
    
3.
Harirchi I, Kolahdoozan S, Karbakhsh M, Chegini N, Mohseni SM, Montazeri A, et al. Twenty years of breast cancer in Iran: Downstaging without a formal screening program. Ann Oncol 2011;22:93-7.  Back to cited text no. 3
    
4.
Mousavi SM, Montazeri A, Mohagheghi MA, Jarrahi AM, Harirchi I, Najafi M, et al. Breast cancer in Iran: An epidemiological review. Breast J 2007;13:383-91.  Back to cited text no. 4
    
5.
Taghavi A, Fazeli Z, Vahedi M, Baghestani AR, Pourhoseingholi A, Barzegar F, et al. Increased trend of breast cancer mortality in Iran. Asian Pac J Cancer Prev 2012;13:367-70.  Back to cited text no. 5
    
6.
Brennan P, McKay J, Moore L, Zaridze D, Mukeria A, Szeszenia-Dabrowska N, et al. Obesity and cancer: Mendelian randomization approach utilizing the FTO genotype. Int J Epidemiol 2009;38:971-5.  Back to cited text no. 6
    
7.
Fawcett KA, Barroso I. The genetics of obesity: FTO leads the way. Trends Genet 2010;26:266-74.  Back to cited text no. 7
    
8.
Wu Q, Saunders RA, Szkudlarek-Mikho M, Serna Ide L, Chin KV. The obesity-associated Fto gene is a transcriptional coactivator. Biochem Biophys Res Commun 2010;401:390-5.  Back to cited text no. 8
    
9.
Calle EE, Kaaks R. Overweight, obesity and cancer: Epidemiological evidence and proposed mechanisms. Nat Rev Cancer 2004;4:579-91.  Back to cited text no. 9
    
10.
Sébert SP, Hyatt MA, Chan LL, Yiallourides M, Fainberg HP, Patel N, et al. Influence of prenatal nutrition and obesity on tissue specific fat mass and obesity-associated (FTO) gene expression. Reproduction 2010;139:265-74.  Back to cited text no. 10
    
11.
Berulava T, Horsthemke B. The obesity-associated SNPs in intron 1 of the FTO gene affect primary transcript levels. Eur J Hum Genet 2010;18:1054-6.  Back to cited text no. 11
    
12.
Gao X, Shin YH, Li M, Wang F, Tong Q, Zhang P. The fat mass and obesity associated gene FTO functions in the brain to regulate postnatal growth in mice. PLoS One 2010;5:e14005.  Back to cited text no. 12
    
13.
Ingman C. Fat mass and obesity associated (FTO) gene involvement in food intake regulation. Uppsala University; 2010.  Back to cited text no. 13
    
14.
Kaklamani V, Yi N, Sadim M, Siziopikou K, Zhang K, Xu Y, et al. The role of the fat mass and obesity associated gene (FTO) in breast cancer risk. BMC Med Genet 2011;12:52.  Back to cited text no. 14
    
15.
Almén MS, Jacobsson JA, Moschonis G, Benedict C, Chrousos GP, Fredriksson R, et al. Genome wide analysis reveals association of a FTO gene variant with epigenetic changes. Genomics 2012;99:132-7.  Back to cited text no. 15
    
16.
Jia G, Yang CG, Yang S, Jian X, Yi C, Zhou Z, et al. Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO. FEBS Lett 2008;582:3313-9.  Back to cited text no. 16
    
17.
Gerken T, Girard CA, Tung Y-CL, Webby1 CJ, Saudek V, Hewitson KS, et al. The Obesity-Associated FTO Gene Encodes a 2-Oxoglutarate-Dependent Nucleic Acid Demethylase. Science. 2007;30:1469-72.  Back to cited text no. 17
    
18.
Kusinska R, Górniak P, Pastorczak A, Fendler W, Potemski P, Mlynarski W, et al. Influence of genomic variation in FTO at 16q12.2, MC4R at 18q22 and NRXN3 at 14q31 genes on breast cancer risk. Mol Biol Rep 2012;39:2915-9.  Back to cited text no. 18
    
19.
Angaji SA, Akashi K, Darvishani S, Azad MS SNP and its applications in treating human diseases. Aust J Basic Appl Sci 2011;5:424-32.  Back to cited text no. 19
    
20.
Eckerman M. Comparison between probe-based TaqMan and HRM detection for SNP analysis considering genotyping of APOE honours. Thesis in Biomedicine, Advanced Level 30 ECTS. School of Life Sciences Skövde University BOX 408 SE-541 28 Skövde Sweden.  Back to cited text no. 20
    
21.
Montazeri A, Sadighi J, Farzadi F, Maftoon F, Vahdaninia M, Ansari M, et al. Weight, height, body mass index and risk of breast cancer in postmenopausal women: A case-control study. BMC Cancer 2008;8:278.  Back to cited text no. 21
    
22.
Rahmati-Yamchi M, Zarghami N, Rahbani M, Montazeri A. Plasma leptin, hTERT gene expression, and anthropometric measures in obese and non-obese women with breast cancer. Breast Cancer (Auckl) 2011;5:27-35.  Back to cited text no. 22
    
23.
Jardé T, Caldefie-Chézet F, Goncalves-Mendes N, Mishellany F, Buechler C, Penault-Llorca F, et al. Involvement of adiponectin and leptin in breast cancer: Clinical and in vitro studies. Endocr Relat Cancer 2009;16:1197-210.  Back to cited text no. 23
    
24.
Available from: http://www.asia.ensembl.org/Homo_sapiens/Variation/Population?db=core;r=16:53807758-53808758;v=rs1477196;vdb=variation;vf=1139083. [Last accessed on 2013 jun 20].  Back to cited text no. 24